Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia
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RESEARCH
Open Access
Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia Anan Xu1†, Rong Li1†, Anbang Ren1†, Haifeng Jian1, Zhong Huang1, Qingxing Zeng1, Baiyao Wang1, Jieling Zheng1, Xiaoyu Chen1, Naiying Zheng1, Ronghui Zheng1, Yunhong Tian1, Mengzhong Liu1,2, Zixu Mao3, Aimin Ji1* and Yawei Yuan1*
Abstract Background: Microglia have been implicated in the pathogenesis of radiation-induced brain injury (RIBI), which severely influences the quality of life during long-term survival. Recently, irradiated microglia were speculated to present an aging-like phenotype. Long noncoding RNAs (lncRNAs) have been recognized to regulate a wide spectrum of biological processes, including senescence; however, their potential role in irradiated microglia remains largely uncharacterized. Methods: We used bioinformatics and experimental methods to identify and analyze the senescence phenotype of irradiated microglia. Western blotting, enzyme-linked immunosorbent assays, immunofluorescence, and quantitative real-time reverse transcription-polymerase chain reaction were performed to clarify the relationship between the radiation-induced differentially expressed lncRNAs (RILs) and the distinctive molecular features of senescence in irradiated microglia. Results: We found that the senescence of microglia could be induced using ionizing radiation (IR). A mutual regulation mode existed between RILs and three main features of the senescence phenotype in irradiated microglia: inflammation, the DNA damage response (DDR), and metabolism. Specifically, for inflammation, the expression of two selected RILs (ENSMUST00000190863 and ENSMUST00000130679) was dependent on the major inflammatory signaling pathways of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). The two RILs modulated the activation of NF-κB/MAPK signaling and subsequent inflammatory cytokine secretion. For the DDR, differential severity of DNA damage altered the expression profiles of RILs. The selected RIL, ENSMUST00000130679, promoted the DDR. For metabolism, blockade of sterol regulatory element-binding proteinmediated lipogenesis attenuated the fold-change of several RILs induced by IR. Conclusions: Our findings revealed that certain RILs interacted with senescence in irradiated microglia. RILs actively participated in the regulation of senescence features, suggesting that RILs could be promising intervention targets to treat RIBI. Keywords: Microglia, Radiation, Senescence, LncRNA, Inflammation, DNA damage response, Metabolism * Correspondence: [email protected]; [email protected] † Anan Xu, Rong Li and Anbang Ren contributed equally to this work. 1 Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No 78, Hengzhigang Road, Yuexiu District, Guangzhou 510095, Guangdong, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons
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